Prognostic Utility of Total 68Ga-DOTATATE-Avid Tumor Volume in Patients With Neuroendocrine Tumors.,Gastroenterology

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Prognostic Utility of Total 68Ga-DOTATATE-Avid Tumor Volume in Patients With Neuroendocrine Tumors.
Gastroenterology ( IF 29.4 ) Pub Date : 2017-11-16 , DOI: 10.1053/j.gastro.2017.11.008
Amit Tirosh ₁ , Georgios Z Papadakis ₂ , Corina Millo ₃ , Dima Hammoud ₃ , Samira M Sadowski ₄ , Peter Herscovitch ₃ , Karel Pacak ₅ , Stephen J Marx ₅ , Lily Yang ₆ , Pavel Nockel ₆ , Jasmine Shell ₆ , Patience Green ₆ , Xavier M Keutgen ₇ , Dhaval Patel ₆ , Naris Nilubol ₆ , Electron Kebebew ₈

Affiliation

Endocrine Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland; Sackler Faculty of Medicine, Tel Aviv University, Israel.
PET Imaging Center, National Institutes of Health Clinical Center, Bethesda, Maryland; Institute of Computer Science (ICS), Foundation for Research and Technology Hellas (FORTH), Crete, Greece.
PET Imaging Center, National Institutes of Health Clinical Center, Bethesda, Maryland.
Endocrine and Thoracic Surgery, University Hospitals of Geneva, Geneva, Switzerland.
National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland.
Endocrine Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
Endocrine Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland; Department of Surgery, Rush University Medical Center, Chicago, Illinois.
Endocrine Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland; Department of Surgery, The George Washington University, School of Medicine and Health Sciences, Washington, District of Columbia.

Background & Aims

Survival times vary among patients with neuroendocrine tumors (NETs) – even among those with the same site, stage, and grade of primary tumor. This makes it difficult to select treatment for patients with unresectable NETs because some patients can survive decades without treatment. ⁶⁸Gallium-DOTATATE positron emission tomography with computed tomography (⁶⁸Ga-DOTATATE PET/CT) is a sensitive imaging technique for detection of NETs. We investigated the prognostic accuracy of ⁶⁸Ga-DOTATATE PET/CT-based analysis of tumor volume in patients with NETs.

Methods

We performed a prospective study of 184 patients with NETs (128 [69.6%] with metastases and 11 patients [6.0%] with locally advanced disease) at the National Institutes of Health Clinical Center (Bethesda, MD) from 2013 through 2017. All patients underwent ⁶⁸Ga-DOTATATE PET/CT image analysis and total ⁶⁸Ga-DOTATATE-Avid tumor volume (⁶⁸Ga-DOTATATE TV) was determined. We also measured fasting serum chromogranin A, neuron-specific enolase, gastrin, glucagon, vasoactive intestinal peptide, pancreatic polypeptide, and 24-hour urinary 5-hydroxyindoleacetic acid levels in all patients. Disease progression was defined as a new lesion or a growth of a known lesion during the interval between baseline ⁶⁸Ga-DOTATATE PET/CT scan and follow-up imaging (14.0 ± 6.1 months; range, 1–35 months). The primary outcomes were progression-free survival (PFS) and disease-specific mortality during a median follow-up time of 18 months (range, 4–35 months).

Results

We found an inverse correlation between quartiles of ⁶⁸Ga-DOTATATE TV and PFS (P = .001) and disease-specific survival (P = .002). A ⁶⁸Ga-DOTATATE TV of 7.0 mL or more was associated with higher odds of disease progression (hazard ratio, 3.0; P = .04). A ⁶⁸Ga-DOTATATE TV of 35.8 mL or more was associated with increased risk of disease-specific death (hazard ratio, 10.6) in multivariable analysis (P = .01), as well as in subgroup analysis of patients with pancreatic NETs.

Conclusions

In a prospective study, we demonstrated the prognostic utility of ⁶⁸Ga-DOTATATE TV in a large cohort of patients with NETs, in terms of PFS and disease-specific mortality.

中文翻译：

总 68Ga-DOTATATE-Avid 肿瘤体积对神经内分泌肿瘤患者的预后效用。

背景与目标

神经内分泌肿瘤 (NET) 患者的生存时间各不相同，即使原发肿瘤部位、分期和级别相同的患者也是如此。这使得无法切除的 NET 患者难以选择治疗方法，因为有些患者无需治疗即可存活数十年。⁶⁸ Ga-DOTATATE 正电子发射断层扫描与计算机断层扫描 ( ⁶⁸ Ga-DOTATATE PET/CT) 是一种用于检测 NET 的灵敏成像技术。^{我们研究了基于68} Ga-DOTATATE PET/CT 的 NET 患者肿瘤体积分析的预后准确性。

方法

我们对 2013 年至 2017 年在国立卫生研究院临床中心（马里兰州贝塞斯达）的 184 名 NET 患者（128 名 [69.6%] 患有转移瘤，11 名患者 [6.0%] 患有局部晚期疾病）进行了一项前瞻性研究。所有患者接受⁶⁸ Ga-DOTATATE PET/CT 图像分析，并确定总⁶⁸ Ga-DOTATATE-Avid 肿瘤体积（^{68 Ga-DOTATATE TV）。}我们还测量了所有患者的空腹血清嗜铬蛋白 A、神经元特异性烯醇化酶、胃泌素、胰高血糖素、血管活性肠肽、胰多肽和 24 小时尿 5-羟基吲哚乙酸水平。^{疾病进展被定义为在基线68} Ga-DOTATATE PET/CT 扫描和后续成像之间的间隔期间（14.0 ± 6.1 个月；范围，1-35 个月）出现新病灶或已知病灶的生长。主要结局是中位随访时间 18 个月（范围 4-35 个月）内的无进展生存期 (PFS) 和疾病特异性死亡率。

结果

^{我们发现68} Ga-DOTATATE TV的四分位数与 PFS ( P = .001) 和疾病特异性生存 ( P = .002) 之间存在负相关。^{7.0 mL 或更多的 68} Ga -DOTATATE TV 与较高的疾病进展几率相关（风险比，3.0；P = .04）。在多变量分析 ( P = .01) 以及胰腺 NET 患者的亚组分析中， 35.8 mL 或更多^{的 68} Ga -DOTATATE TV 与疾病特异性死亡风险增加相关（风险比为 10.6）。